PSVIII-15 Genome wide DNA methylation analysis reveals role of DNA methylation in cow’s ileal response to Mycobacterium avium subsp. paratuberculosis
Bibliographic record
Abstract
Abstract Several investigations on disease progression of Mycobacterium avium subsp. paratuberculosis (MAP) infection in dairy cows have revealed molecular mechanisms including genes and pathways implicated in MAP pathogenesis. Epigenetic processes including DNA methylation are known to regulate the expression of genes and many biological processes. However, limited studies have examined the role of DNA methylation in the pathogenesis of Johne’s disease (JD). This study examined the impact of subclinical MAP infection on DNA methylation profile in the ileum of cows, the site of initial interaction between MAP and host. DNA from ileum tissues from five cows positive for MAP (direct fecal qPCR and blood ELISA test; MAP+/+) and 5 cows negative for MAP (MAP-/-) were subjected to whole genome bisulfite sequencing and bioinformatics analysis. 2000 differentially methylated cytosines (DMCs; FDR< 0.05) and 205 differentially methylated regions (DMRs; P < 0.01) were detected. Majority of DMCs and DMRs are located in intergenic regions (87.2% and 57.1%) followed by intronic regions (12.8% and 30.7%) of genes, respectively. Some DMCs are located on 250 genes including genes that were previously identified to be associated with JD (e.g. IL-12RB2, CD38). Interestingly, CD38, known to play roles in the effective containment of mycobacteria within granulomata in cows and genetic polymorphisms in IL-12RB2 are associated with JD and human Crohn’s disease. Also, several genes of the solute carrier family including SLC13A3, SLC15A1, SLC17A7, SLC25A21, SLC25A38 and SLC9A9 harbored DMCs. Some members of this gene family participate in pathogen clearance and have associations with JD. Our data suggest that DNA methylation changes may have regulatory roles in host (ileum) response to MAP infection. Our data therefore suggest that DNA methylation changes contribute to the regulation of host response to MAP pathogenesis and may be one of the mechanisms that MAP uses to subvert host immune responses for its survival.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".